HtrA2 is up-regulated in the rat testis after experimental cryptorchidism

AIM: The aim of the present study was to elucidate the role of high temperature requirement A2 (HtrA2) in germ cell loss in the heat-stressed testis. METHODS: We examined the expression of HtrA2, caspase-9 activity and proteolytic activity of HtrA2 in the rat testis, and their in vivo responses to experimental cryptorchid treatment. RESULTS: Northern analysis revealed the expression of HtrA2 mRNA peaked at days 1 and 7 after cryptorchid treatment. While expression of HtrA2 mRNA was seen in the spermatogonium, spermatocytes and some spermatids in normal adult rat testis, experimental cryptorchidism treatment resulted in a marked increase in its signal intensity in spermatocytes and some spermatids, and the layers of spermatogonium and early primary spermatocytes became negative at days 1 and 7 after the treatment. However, the spermatogonium, Sertoli cells and interstitial cells appeared to have strong intensities at days 14, 28 and 56 after the treatment. Western analysis revealed the expression of HtrA2 protein peaked at day 2 coinciding with the increase of positive spermatogonium, the appearance of protein-positive interstitial cells, and day 28 coinciding with the reappearance of protein-positive interstitial cells. Caspase-9 activity peaked at day 2 and HtrA2 proteolytic activity peaked at day 28. Consequently, the first peak of HtrA2 mRNA expression was followed by the peak of caspase-9 activity and the second peak was followed by the peak of proteolytic activity; however, the second peak of mRNA expression had considerable chronological difference from that of the protein. CONCLUSION: These findings suggest the probabilities that the heat stress results in germ cell death by a caspase-independent manner with the elevation of HtrA2 proteolytic activity, as well as a caspase-dependent manner with the elevation of caspase-9 activity.     

11C-choline positron emission tomography in bladder cancer: Report of four cases

Little work has been done with positive emission tomography (PET) in bladder tumors because high urinary excretion of (18)F-FDG makes visualization of the bladder tumor difficult. (11)C-choline has recently been reported as a new tracer which lacks urinary radioactivity. We report the result of (11)C-choline PET in four patients with invasive bladder tumors. In one case, (11)C-choline PET could detect bladder tumor effectively without urinary activity and bone metastasis despite negative bone scintigraphy. On the other hand, an intense accumulation of the tracer in the bladder hampered the interpretation on PET scanning in three patients. The mechanisms of the (11)C-choline accumulation in the bladder were reported to be due to inflammatory and proliferative changes in the mucosa of the bladder from previous catheterization or other factors. Further study is necessary to prove the value of (11)C-choline PET for detecting primary bladder cancer and bone metastasis.     

A protease inhibitor attenuates gastric erosions and microcirculatory disturbance in the early period after thermal injury in rats

The effects of camostat mesilate, a synthetic serine protease inhibitor on gastric microcirculation and active oxygen species generated by leucocytes from the gastric and jugular veins in the early period after thermal injury were assessed. Male Wistar rats were anaesthetized and a 30% full skin-thickness dorsal burn was inflicted. Camostat mesilate (100 mg/kg) was dissolved in distilled water and administered orally to rats 40 min before thermal injury (the camostat group). The control animals (the vehicle group) were administered distilled water orally. Rolling leucocytes as well as Monastral blue B deposits in venules were observed using in vivo microscopy. Active oxygen species were measured by chemiluminescence. Camostat mesilate decreased the total length of gastric erosion, venular deposits of Monastral blue B, and rolling of leucocytes in venules, and relatively increased luminol-dependent chemiluminescence activity generated by zymosan-stimulated leucocytes 15 min after thermal injury. These results suggest that serine proteases are involved in the formation of gastric erosions and gastric microcirculatory disturbance in the early period after thermal injury.     

Oral Tolerance Induced by Enterobacteria Altered the Process of Lymphocyte Recruitment to Intestinal Microvessels: Roles of Endothelial Cell Adhesion Molecules,TGF‐beta and Negative Regulators of TLR Signaling

Objective: Although enterobacteria are implicated in intestinal immune response, there has been no report on how intraluminal pathogens affect lymphocyte recruitment. The aim of this study was to determine how the presence of intestinal flora affects lymphocyte migration to intestine under physiological and lipopolysaccharide (LPS)‐induced inflammatory conditions. Methods: Interaction of T‐cells with ileal microvessels was monitored by using an intravital microscope in mice under germ‐free (GF) and specific pathogen‐free (SPF) conditions. LPS was administered into either the peritoneal cavity or duodenum before lymphocyte injection. Results: Adherence of T‐cells was greater in SPF than in GF mice, indicating that the presence of enterobacteria upregulated migration under physiological conditions. Intraperitoneally administered LPS significantly increased the adherence of T‐cells in both GF and SPF mice accompanied by the expression of adhesion molecules and proinflammatory cytokines. However, intraluminally administered LPS did not enhance the adherence of T‐cells in SPF mice. A significant induction of increase in mRNA expression of IRAK‐M, a negative regulator of TLR4 signaling, and transforming growth factor beta (TGF‐beta), a regulatory cytokine, was observed in SPF mice after luminal LPS treatment. Conclusions: Tolerance to intraluminally administered LPS in the lymphocyte recruitment process was induced by enterobacteria, possibly via the induction of IRAK‐M and TGF‐beta.     

Effectiveness of prosthetic mandibular advancement for obstructive sleep apnea:Analysis by sleep position

Abstract Fifteen patients with obstructive sleep apnea were treated using prosthetic mandibular advancement (PMA). Each patient was evaluated in the supine and lateral decubitus positions with and without PMA. After PMA treatment, the mean intraesophageal pressure (Peso) in the supine position improved from -42.6 to -27.3 cmH₂O and the mean apnea + hypopnea index (AHI) decreased from 48.8/h to 23.7/h. The mean Peso in the lateral decubitus position improved from -27.9 to -18.6 cmH₂O and the mean AHI decreased from 9.6/h to 6.6/h. With PMA, respiratory disturbance during sleep further improved by changing the body position from the supine to lateral decubitus position.     

Histoclinical Long-standing Follow-up Study of Hyperplastic Polyps of the Stomach

In a series of 2,013 gastric polyps in 1,201 patients, morphological and histopathological studies have been performed. Ninety-three hyperplastic polyps in 56 patients have been followed-up endoscopically and histopathologically for five to 12 years. The incidence of detection of gastric polyps has increased: 1.4% in 1967 to 8.7% in 1979 year by year. Thirty patients (54%) among the 56 showed changes in number, size or shape of polyps during follow-up. Twenty patients (37%) revealed numerical changes (increase in 16 patients, reversion in three patients and vanishing in two patients).
Twenty-eight polyps (30%) showed morphological changes, six of them showed continuous enlargement, 18 lesions repeated enlargement, stationary or reduction stages, three lesions were reversed and two polyps disappeared.
Histopathologically, three lesions showed transformation from the hyperplastic type to adenoma while demonstrating morphological enlargement. Two of these showed increase in cellular atypia, from the hyperplastic type through adenoma with severe atypia and finally to carcinoma in the polypectomy specimens. From this study, it was concluded that although hyperplastic polyps show changes in size, shape or number with passage of time, malignant changes occur in only a few cases.     

Effectiveness of tonsillectomy in adult sleep apnea syndrome

Abstract Tonsillectomy was performed on 10 adult sleep apnea patients (five males, five females; average age, 39 years old; average body mass index, 24.8 kg/m²). Tonsillectomy alone was indicated if tonsillar hypertrophy was moderate to severe and the length of the soft palate was less than 35 mm according to cephalometry. Remarkable improvements were observed in all cases following surgery. The average weight of the resected tonsils was 11 g. The patients demonstrated a preoperative apnea + hypopnea index (AHI) of 14.4/h. This decreased to 2.9/h postoperatively. The intraesophageal pressure change improved from -36.6 to -15.7 cmH₂O following surgery. A significant correlation between preoperative AHI and the degree of obesity ( r = 0.684, P < 0.05) was found. Although uvulopalatopharyngoplasty has been used extensively to treat sleep apnea, the present results suggests that certain subjects can be effectively treated through only tonsillectomy.     

Modulation of intestinal immune system by dietary fat intake: Relevance to Crohn's disease

Gut-associated lymphoid tissue is the major inductive site of the mucosal immune system, which is functionally independent of the systemic immune system. Both the amount and type of dietary fat modulate intestinal immune function. Absorption of long-chain fatty acids stimulates lymphocyte flux and lymphocyte blastogenesis in intestinal lymphatics. Long-chain fatty acid absorption also significantly enhances migration of T lymphocytes to Peyer's patches, possibly due to up-regulation of adhesion molecules, such as α4-integrin and L-selectin. Lipoproteins are involved in stimulation of lymphocyte function by both receptor-dependent and independent mechanisms. However, unsaturated fatty acids at higher concentrations have a suppressive effect on cell-mediated immunity via eicosanoid release, receptor affinity changes or interactions with intracellular signal transduction. Fat absorption also influences various other cells in the intestinal mucosa: increased cytokine release from intestinal epithelial cells follows long-chain fatty acid absorption. In Crohn's disease, elemental diets and total parenteral nutrition often induce remission, possibly by reducing antigenic load on activated immune cells in the intestine and, thus, down-regulating hyperreactive CD4 cells. Dietary oleic acid supplements caused an immunological reversal effect in the intestinal immune system of animals fed an elemental diet. An excess of long-chain fatty acids in an elemental diet, therefore, may negate its beneficial effect on gut-associated lymphoid tissues in Crohn's disease. In contrast, supplemental dietary fish oil apparently tends to prevent relapse of Crohn's disease. Because dietary fat intake is closely associated with immunological function of the intestinal mucosa, careful manipulation of dietary fat can be important in management of this disease.     

Cystic hamartoma of the renal pelvis

Cystic hamartoma of the renal pelvis is a rare benign tumor in the same category as mixed epithelial and stromal tumors. We present a 33-year-old woman with a solid and cystic intrarenal tumor extending into the renal pelvis. She underwent radical nephrectomy and ureterectomy under the diagnosis of renal tumor or renal pelvic tumor. Histopathologically, the tumor was composed of a biphasic proliferation of epithelial and mesenchymal elements. We believe the present case is best classified as a cystic hamartoma of the renal pelvis in the category of mixed epithelial and stromal tumors because of the coexistence of hamartomatous lesions, such as the proliferation of adipose cells and well to poorly differentiated fibromuscular lesions.